The present project is concerned with an investigation of the genetic basis of DNA repair and mutagenesis in the complex eucaryote, Drosophila melanogaster. The experimental approach, patterned after recent procaryotic studies, seeks to identify genes involved with repair and mutagenesis on the basis of mutagen sensitivity. Variations of standard Drosophila methods have led to the isolation of forty-nine X-linked mutants which display an increased sensitivity to killing by the alkylating mutagen, methyl methanesulfonate (MMS). Analysis of twenty-eight of these strains has resulted in the identification of six complementation groups and these complementation groups have been localized to six separable loci. Mutants at four of these loci confer enhanced sensitivity to MMS, X-rays and ultraviolet light while mutants at the other two loci yield increased sensitivity to MMS and X-rays. Female sterility appears to be associated with many of the mutants and preliminary tests indicated associated meiotic difficulties. One of these mutants has been shown to exhibit mitotic chromosome instability and to be defective in postreplication repair. Current experiments are concerned with multiple mutant analyses for determinations of hypothetical repair pathways and large-scale mutagenesis experiments to determine the effect of the various mutations on spontaneous and induced mutagenic events. BIBLIOGRAPHIC REFERENCES: Smith, P. Dennis. 1976. Mutagen sensitivity of Drosophila melanogaster. III. X-linked loci governing sensitivity to methyl methanesulfonate. Molecular and General Genetics 149: 73-85. Baker, Bruce S. inter alia P. Dennis Smith. 1976. Genetic controls of meiotic recombination and somatic DNA metabolism in Drosophila melanogaster. Proc. Natl. Acad. Sci., U.S.A. 73: 4140-4144.